PMID- 30186184
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - Inflammasome-Independent NALP3 Contributes to High-Salt Induced Endothelial 
      Dysfunction.
PG  - 968
LID - 10.3389/fphar.2018.00968 [doi]
LID - 968
AB  - Backgrounds and Aims: Na(+) is an important nutrient and its intake, mainly from 
      salt (NaCl), is essential for normal physiological function. However, high salt 
      intake may lead to vascular injury, independent of a rise in blood pressure (BP). 
      Canonical NALP3 inflammasome activation is a caspase-1 medicated process, 
      resulting in the secretion of IL-18 and IL-1beta which lead to endothelial 
      dysfunction. However, some researches uncovered a direct and 
      inflammasome-independent role of NALP3 in renal injury. Thus, this study was 
      designed to investigate the possible mechanisms of NALP3 in high salt induced 
      endothelial dysfunction. Methods and Results: Changes in endothelial function 
      were measured by investigating mice (C57BL/6J, NALP3(-/-) and wild-type, WT) fed 
      with normal salt diet (NSD) or high salt diet (HSD) for 12W, and thoracic aortic 
      rings from C57BL/6J mice cultured in high-salt medium. Changes of tube formation 
      ability, intracellular reactive oxygen species (ROS), and NALP3 inflammasome 
      expression were detected using mouse aortic endothelial cells (MAECs) cultured in 
      high-salt medium. Consumption of HSD for 12W did not affect BP or body weight in 
      C57BL/6J mice. Endothelium-dependent relaxation (EDR) decreased significantly in 
      C57BL/6J mice fed with HSD for 12W, and in isolated thoracic aortic rings 
      cultured in high-salt medium for 24 h. Results from the aortic ring assay also 
      revealed that the angiogenic function of thoracic aortas was impaired by either 
      consumption of HSD or exposure to high-salt medium. NALP3(-/-) mice fed with HSD 
      showed a relatively mild decrease in EDR function when compared with WT mice. 
      Tube length of thoracic aortic rings from NALP3(-/-) mice was longer than those 
      from WT mice after receiving high-salt treatment. Inhibiting NALP3 with a NALP3 
      antagonist, small interfering (si) RNA experiments using si-NALP3, and 
      decomposing ROS significantly improved tube formation ability in MAECs under high 
      salt medium. NALP3 expression was increased in MAECs cultured with high salt 
      treatment and inhibiting NALP3 reversed the down-regulation of p-eNOS induced by 
      high salt in MAECs. Conclusion: High salt intake impairs endothelial function, 
      which is at least in part mediated by increasing NALP3 expression.
FAU - Fu, Hui
AU  - Fu H
AD  - Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Chen, Ji-Kuai
AU  - Chen JK
AD  - Department of Health Toxicology, Faculty of Naval University, Second Military 
      Medical University, Shanghai, China.
FAU - Lu, Wen-Jie
AU  - Lu WJ
AD  - Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Jiang, Yu-Jie
AU  - Jiang YJ
AD  - Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Wang, Yuan-Yuan
AU  - Wang YY
AD  - Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Li, Dong-Jie
AU  - Li DJ
AD  - Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Shen, Fu-Ming
AU  - Shen FM
AD  - Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20180822
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6113916
OTO - NOTNLM
OT  - NALP3
OT  - angiogenic function
OT  - endothelial-dependent relaxation
OT  - high salt intake
OT  - reactive oxygen species
EDAT- 2018/09/07 06:00
MHDA- 2018/09/07 06:01
PMCR- 2018/08/22
CRDT- 2018/09/07 06:00
PHST- 2017/11/02 00:00 [received]
PHST- 2018/08/06 00:00 [accepted]
PHST- 2018/09/07 06:00 [entrez]
PHST- 2018/09/07 06:00 [pubmed]
PHST- 2018/09/07 06:01 [medline]
PHST- 2018/08/22 00:00 [pmc-release]
AID - 10.3389/fphar.2018.00968 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Aug 22;9:968. doi: 10.3389/fphar.2018.00968. eCollection 
      2018.